CARDIOVASCULAR JOURNAL OF AFRICA • Vol 24, No 3, April 2013
AFRICA
97
Higher statin doses linked to acute kidney injury: South African
experts comment on clinical implications
A meta-analysis published recently in
the
British Medical Journal
has linked
higher doses of statins (resulting in at
least a 45% reduction in low-density
lipoprotein cholesterol) to a higher risk of
acute kidney injury (AKI) in the first four
months of therapy compared to lower-
dose statins.
1
The study was based on data from
Canadian, UK and USA databases of
some two million patients, where each
index case of AKI was matched with 10
controls from the same database and also
matched in terms of time of initiation
of therapy. Patients were judged to be
treated with higher statin doses if they
were given
≥
10 mg rosuvastatin,
≥
20
mg atorvastatin and
≥
40 mg simvastatin.
The rate ratio of hospitalisation for
AKI for users of high-potency versus
low-potency statins was 1.34 (95% CI:
1.25–1.43) for those without a chronic
kidney disease (CKD) history and a
non-significant 1.10 (95% CI: 0.99–1.23)
for those with a CKD history.
CVJAfrica asked two South
African experts for their
comments on the study:
Prof Brian Rayner, hypertension
and renal expert, University of Cape
Town, and Dr Dirk Blom, lipid expert,
University of Cape Town
Prof Brian Rayner
The risks of acute kidney injury were
shown to be raised by 34% over the
first four months. This sounds large, but
translates to only one extra acute kidney
injury event per 1 700 patients treated
with the higher dose.
The difficulties of interpreting meta-
analyses of this kind are well known
as they group together patients with
different co-morbidities and perhaps
different predispositions to AKI, although
this study did try to match index cases to
appropriate controls.
There were important differences in
demographics in the high-dose statin
group, with more heart failure and
more use of ARBs and ACE inhibitors,
factors well known to predispose to AKI.
Additionally there are no data in the use
of contrast between the groups, which is
a major omission from the article. This
could account for the higher incidence in
the first 120 days, especially in patients
treated for secondary prevention requiring
coronary angiograms.
For the clinician there are also no data
on the causes and severity of AKI, which
would be useful in determining causation
in the high-dose group. Additionally
AKI can range from a 25% increase in
creatinine level to life-threatening renal
failure requiring dialysis.
Dr Dirk Blom
Observational database studies rely on the
accuracy and completeness of diagnostic
coding; in this case the coding for acute
kidney injury. Because this is a database
study, we do not know the context in
which higher statin doses were prescribed,
e.g. were statin doses increased following
an intervention (contrast administration)
or cardiovascular event. We also do not
know much about the severity of the
kidney injuries observed.
Observational studies are prone to
confounding (e.g. sicker patients are
prescribed more therapy) and although
the authors adjusted their data by using
propensity scoring, a residual risk of
confounding remains. Patients on high-
dose statins had higher rates of congestive
cardiac failure (not sufficiently different
to account for the observed effect on
AKI) and were more likely to use ACE
inhibitors, ARBs, loop diuretics and beta-
blockers.
This study showed no statistically
significant harm with the higher dose of
statins given to patients with CKD. This
is certainly at odds with expectations, as
CKD patients would be more vulnerable
to any potential renal effects of the ‘more-
potent statins’.
Our clinical recommendations for
daily practice are:
•
We would not change therapy at the
moment, i.e. continue patients who are
on high doses on their current therapy
if indicated.
•
Be alert that there may be a small
excess risk of AKI in those on high-
dose statin therapy and avoid nephro-
toxic medications or interventions.
•
Clinical judgement is required when
choosing a statin; the clinician needs
to balance cardiovascular risk, lipid
profile and potential statin side effects.
•
Statin therapy has known benefits and
should not be withheld because of
fears of AKI. The absolute risk of AKI
remains very low
•
Clinicians should not lose sight of the
fact that admission rates for AKI are
markedly higher in those with CKD
than those with no CKD (the differ-
ence varies by database but the rate
is at least tenfold and often greater).
The risk of AKI in those with CKD is
therefore, a major concern and statins
do not pose a specific threat here.
Focus on good management of those
with CKD to avoid precipitating acute
kidney injury. This will likely be the
intervention that has the largest bene-
fit. The absolute risk increase for AKI
from high-dose statins is very small in
those without CKD when compared to
the very high baseline risk of AKI in
those with CKD.
•
There have been reports of proteinuria
with high-dose statins (especially with
very high doses, such as rosuvastatin
80 mg/day, which was subsequently
not marketed).
•
Other observational studies have also
shown an increased risk of AKI with
statin therapy, but observational data
are not well suited to causality analyses.
J Aalbers
1.
Dormuth CR, Hemmelgarn BR, Paterson JM,
James MT,
et al.
Use of high potency statins
and rates of admission for acute kidney
injury: multicentre, retrospective observa-
tional analysis of administrative databases.
Br Med J
2013;
346
: 1880. doi:10.1136/bmj.
f880 (published 20 March 2013).
